Recommendations for the Reporting of Tissues Removed As Part of The

Recommendations for the Reporting of Tissues Removed as Part of the Surgical Treatment of Common Malignancies of the Eye and its Adnexa Robert Folberg, M.D., Diva Salomao, M.D., Hans E. Grossniklaus, M.D., Alan D. Proia, M.D., Ph.D., Narsing A. Rao, M.D., J. Douglas Cameron, M.D. University of Illinois at Chicago (RF), Chicago, Illinois; The Mayo Clinic (DS, JDC), Rochester, Minnesota; Emory University (HEG), Atlanta, Georgia; Duke University (ADP), Durham, North Carolina; and The Keck School of Medicine (NAR)-University of Southern California, Los Angeles, California

The purpose of these recommendations is to pro- The Association of Directors of Anatomic and Sur- vide an informative report for the clinician. The gical Pathology developed recommendations for the recommendations are intended as suggestions, and surgical pathology report for common malignant adherence to them is completely voluntary. In spe- tumors. The recommendations for tumors of the cial circumstances, the recommendations may not eye and its adnexa are reported. be applicable. The recommendations are intended as an educational resource rather than a mandate. KEY WORDS: Basal cell carcinoma, Conjunctiva, Eyelid, Melanoma, Orbit Retinoblastoma, Seba- ceous carcinoma, Squamous cell carcinoma, Uvea. BACKGROUND Mod Pathol 2003;16(7):725–730 Before the public awareness of AIDS and Alzhei- The Association of Directors of Anatomic and mer’s disease as health problems, the disease Surgical Pathology named several committees to feared most by Americans was cancer; the second develop recommendations about the content of the most feared condition was blindness (The Gallup surgical pathology report for common malignant Organization, Inc., Public knowledge and attitudes tumors. A committee of persons with special inter- concerning blindness—a survey sponsored by Re- est and expertise write the recommendations, search to Prevent Blindness, Inc., New York, Octo- which are reviewed and approved by the council of ber 1965 and April 1976, unpublished data). Pa- Association of Directors of Anatomic and Surgical tients who are confronted with a diagnosis of ocular Pathology and subsequently by the entire cancer, therefore, face two of their most principal membership. fears: shortening of their lifespan and loss of vision. The recommendations have been divided into Ophthalmologists who manage most patients with four major areas: 1) items that provide an informa- ocular malignancies often try to balance the pa- tive gross description; 2) additional diagnostics fea- tient’s desire to preserve vision with the goal of tures recommended for inclusion in every report if eradicating the cancer. In general, the pathologist’s possible; 3) optional features that may be included report should catalog not only those features ap- in the final report; and 4) a checklist. propriate for estimating the natural history of the patient’s disease (prognosis), but also those features that might compromise vision.

Copyright © 2003 by The United States and Canadian Academy of In general, it is recommended that pathologists Pathology, Inc. report on malignancies of the orbit using formats VOL. 16, NO. 7, P. 725, 2003 Printed in the U.S.A. Date of acceptance: February 26, 2003. either published or in development for the coun- The authors were the members of an ad hoc committee of the Association terpart lesion elsewhere in the body. For example, of Directors of Anatomic and Surgical Pathology chaired by Robert Fol- berg, M.D., Chicago, Illinois. lymphomas of the orbit should be reported accord- Address reprint requests to: Robert Folberg, M.D., University of Illinois at ing to generalized recommendations for reporting Chicago, Department of Pathology (MC 847), 1819 West Polk Street, Room 446, Chicago, IL 60612-7335. lymphomas. It is reasonable for the report for rhab- Note: Ophthalmic pathologists use the term “primary acquired melanosis domyosarcoma (the most common primary malig- with atypia” in place of the following terms: intraepithelial atypical melanocytic hyperplasia, malignant melanoma in situ, Level I malignant nancy of the orbit in childhood in the United melanoma. States) to follow recommendations for reporting DOI: 10.1097/01.MP.0000076978.06324.EE rhabdomyosarcomas in general. The lacrimal gland

725 may be considered to be a minor salivary gland for 7. Orientation of the lesion if provided by the the purposes of reporting malignancies in this re- surgeon gion, and pathology reports dealing with lacrimal 1. Some surgeons will identify surgical margins of gland malignancies (principally adenoid cystic car- interest by applying a suture to an edge of the cinoma) should follow recommendations for re- specimen, by painting certain margins with dyes, or porting this tumor as described for the salivary attaching the specimen to a piece of filter paper and gland. making notations on the specimen mount Recommendations are therefore offered for three B. Iridectomy/iridocyclectomy classes of ocular malignancies: conjunctival neo- 1. Dimensions of the specimen (length, width, plasms (including those affecting the limbus—the thickness) junction between the cornea and sclera), sebaceous 2. Description of tissue received (iris only, iris and carcinoma (a common malignancy of the eyelid), ciliary body, iris, ciliary body and peripheral cornea and the two major intraocular neoplasms (retino- and/or sclera including location by clock hour) blastoma and malignant melanoma). 3. Dimensions of lesion (length, width, height) 1. General –the Association recommends that the 4. Measurement of minimum distance between following features be included in the final report edge of lesion and surgical margin (minimum because they are generally accepted as being of clearance) prognostic importance, of visual importance, re- 1. Relevant surgical margins include the lateral quired for staging or therapy, and/or traditionally margins and the posterior margin (the anterior expected. margin is the pupillary border and is not a true A. How the specimen was received (e.g., fresh or surgical margin) in fixative) C. Enucleation B. How the specimen was identified (e.g., labeled 1. Dimensions of the eye (anterior-posterior, hor- with the name, medical record number, and sur- izontal, vertical) geon’s name) 2. Length of optic nerve attached C. Laterality of the lesion (e.g., originating from 3. Examination of the surface of the eye for gross the right or left eye) evidence of extraocular extension of tumor D. The exact anatomic location of the tumor 4. Dimensions of the cornea (horizontal and 1. Conjunctiva: bulbar (by quadrant –superior, vertical) inferior, nasal, temporal), palpebral (superior or in- 5. Clarity of the cornea ferior), fornix (superior or inferior) 6. Color of the iris (describe lesions if present) 2. Limbus (by clock hour) 7. Shape and diameter of the pupil 3. Caruncle or plica semilunaris 8. Transillumination of the eye with dimensions 4. Eyelid (upper, lower, medial canthus, lateral of any shadows canthus) 1. Transillumination of the eye may be performed 5. Intraocular tissue (iris, ciliary body –by clock with a fiberoptic light source to locate a tumor hour) within the eye by the shadow that it casts during E. The type of surgical procedure this procedure 1. Incisional biopsy, excisional biopsy, shave bi- 1. Location of transillumination shadow(s) rela- opsy (conjunctiva, eyelids) tive to the limbus and optic nerve (distance of 2. Iridectomy (removal of iris tissue), iridocyclec- shadow borders from limbus and optic nerve) tomy (removal of iris and ciliary body tissue) 2. Location of the shadow relative to clock hour 3. Enucleation (removal of eye) 9. Describe the section plane used to open the 4. Exenteration (removal of the eye and orbital eye contents, with or without eyelids, not covered in 10. Obtain cross section of the optic nerve this report) 1. Retinoblastoma 2. Gross Description 1. Obtain a section from either the surgical mar- A. Conjunctival and Eyelid Biopsy gin of the optic nerve (the transected edge) or the 1. Dimensions of the specimen (length, width, cut surface of the optic nerve as it inserts in the eye thickness) 1. If the cut section of the optic nerve adjacent to 2. Maximum diameter of any visible lesion the eye is negative for tumor, then one may con- 3. Measurement of minimum distance between clude that there is no involvement of the nerve edge of lesion and surgical margin (minimum posterior to the eye (tumor extends through the clearance) nerve without skip lesions) 4. Presence or absence of ulceration 2. Frequently, the surgical margin of the optic 5. Color of the lesion and adjacent tissue nerve (the cut edge of the nerve) is crushed by 6. Description of attached tissue (episclera, enucleation scissors cornea) 11. Describe the cut surface of the eye

726 Modern Pathology 1. Retinoblastoma modification of the Breslow method using a cali- 1. Number and size of lesions brated ocular micrometer. The tumor thickness is 2. Location of the lesion(s) measured from the top of the epithelium (there is 3. Gross evidence of choroidal invasion or ex- no granular layer in the normal conjunctival traocular extension epithelium). 4. Presence or absence of vitreous seeding 1. Some pathologists consider a depth of invasion 5. Presence or absence of retinal detachment of 0.8 mm to be significant in separating patients at 2. Uveal melanoma high risk for metastasis from those at low risk. 1. Tissues involved (choroid only, choroid and 4. Intralymphatic invasion by tumor ciliary body, ciliary body only, iris and ciliary body, 5. Optional criteria iris only) 1. Mitotic figures/mm2; proliferation indices us- 2. Location of the melanoma relative to clock ing markers such as MIB-1 or Ki67 hour C. Sebaceous carcinoma of the eyelid 3. Dimensions from cut surface (maximum zone 1. Location of the tumor (upper eyelid versus of scleral contact, dimension perpendicular to max- lower eyelid) imum zone of scleral contact, elevation measured 2. Size in millimeters from top of lesion to interface with sclera) 1. Some pathologists consider this measurement 4. Color of the surface lesion to be optional 1. Color of the lesion may provide important clin- 3. Gland of origin (Meibomian versus Zeis gland) icopathologic correlations to the ophthalmologist 4. State presence or absence of infiltrative growth 1. A white plaque over the surface of the lesion pattern may indicate fibrous metaplasia of the overlying 5. Differentiation retinal pigment epithelium 1. Some pathologists consider the differentiation 2. Orange pigment over the surface of the tumor of sebaceous carcinoma to be an optional feature of (lipofuscin) is considered by some ophthalmolo- the report gists as clinical evidence of an aggressive tumor 6. Multicentricity 5. Color of the cut surface of the lesion (melanot- 7. Intraepithelial (intraepidermal) pagetoid in- ic, amelanotic, variegated) volvement in conjunctiva, cornea, or eyelid skin 6. Presence or absence of retinal detachment or 8. Tumor involvement of lymphatics or blood hemorrhage vessels or intraorbital invasion 7. Presence or absence of extraocular extension 9. State presence or absence of tumor at resection or involvement of intrascleral emissary channels margins, including the deep margin and all lateral 3. Microscopic Description margins (description of margins should include A. Conjunctival squamous cell carcinoma presence or absence of intraepithelial pagetoid 1. State presence or absence of invasion into un- spread) derlying tissues (episclera, corneal stroma) D. Retinoblastoma 2. State presence or absence of tumor at resection 1. Growth pattern (diffuse, unifocal, multifocal) margins, including the deep margin and all lateral 2. Bilaterality and trilaterality (bilateral with in- margins volvement of the pineal gland) 3. State degree of differentiation (well differenti- 3. Differentiation (presence of Flexner- ated, moderately differentiated, poorly Wintersteiner rosettes, Homer Wright rosettes, and differentiated) fleurettes) 4. State type (ordinary squamous cell carcinoma, 4. Invasion into the optic nerve by layer (prelami- spindle cell variant of squamous cell carcinoma, nar, laminar, retrolaminar, to optic nerve resection mucoepidermoid carcinoma) margin) 5. Mention presence or absence of vascular, lym- 5. Extraocular extension phatic, perineural, intraocular, or intraorbital 6. Some pathologists and oncologists consider invasion choroidal invasion to be a significant risk factor for B. Conjunctival malignant melanoma metastasis although this feature is not universally 1. State presence or absence of invasion into un- accepted as prognostically significant derlying issues (episclera, corneal stroma) 7. Optional features of the tumor 2. State presence or absence of tumor at resection A. Endophytic vs. exophytic, presence and degree margins, including the deep margin and all lateral of tumor necrosis, calcification, DNA deposition margins (description of margins should include around blood vessels, vitreous seeding, anterior presence or absence of intraepithelial primary ac- chamber seeding (pseudohypopyon) quired melanosis with atypia, see note) 8. Effects of the tumor on the eye 3. Thickness of the tumor in millimeters and A. Retinal detachment; iris neovascularization tenths of millimeters as measured by the Jakobiec E. Uveal malignant melanoma

Reporting Tissues Removed as Part of Surgical Treatment (R. Folberg et al.) 727 1. Location (confined to the iris, involving the iris TABLE 1. Checklist for Conjunctival Squamous Cell Carcinoma and ciliary body, confined to the ciliary body, involving the ciliary body and choroid, involving the 1. Site (circle all affected) Conjunctiva iris, ciliary body and choroid, or confined to the Bulbar, palpebral, fornix choroid) Caruncle 2. Extraocular extension Plica semilunaris Limbus 3. Growth pattern: diffuse melanoma, ring mela- Cornea noma, focal melanoma 2. Procedure 4. Cell type (McLean’s modification of the Cal- Excisional biopsy Incisional biopsy lender classification) Debridement of corneal epithelium 5. Mitotic figures per 40 high-power fields 3. Involvement of the (circle all that apply) 6. Presence or absence of 100 tumor infiltrating Corneal stroma Episclera lymphocytes per 20 high-power fields Orbital fat 7. Matrix-rich microcirculation-associated loops, 4. Type (circle one) networks or parallel with cross-linking structures Squamous cell carcinoma, common type Spindle cell variant, squamous cell carcinoma (some pathologists have suggested that microvas- Acantholytic variant, squamous cell carcinoma cular density is also a prognostic feature) Mucoepidermoid carcinoma 8. Optional features 5. Excision (circle one) Complete A. Pertaining to the tumor: presence of absence Not complete laterally (indicate affected margins) but complete in of nevus, necrosis, intrascleral invasion, invasion depth into the trabecular meshwork, or invasion into the Not complete in depth but complete laterally Not complete either laterally or in depth vortex veins; cytomorphometric measurement of 6. Vascular invasion (circle one) nucleolar diameter (mean of the largest nucleoli or Absent standard deviation of nucleolar area), proliferation Blood vessels Lymphatics indices, cytogenetic abnormalities (especially chro- Blood vessels and lymphatics mosomes 3 and 8) B. Effects of the tumor on the eye: retinal detachment, Bruch’s membrane rupture, retinal invasion, TABLE 2. Checklist for Conjunctival Melanoma iris neovascularization, angle closure, cataract 1. Site (circle all affected) Conjunctiva Bulbar, palpebral, fornix Examination of Ocular Tissues Caruncle 1. Torczynski E. Preparation of ocular specimens Plica semilunaris Limbus for histopathologic examination. Ophthalmology Cornea 1981;88:1367–71. 2. Procedure 2. Folberg R, Verdick RE, Weingeist TA, Montague Excisional biopsy Incisional biopsy PR. Gross examination of eyes removed for choroi- Debridement of corneal epithelium dal or ciliary body melanoma. Ophthalmology 3. Involvement of the (circle all that apply) 1986;93:1643–7. Corneal stroma Episclera Orbital fat Conjunctival Squamous Cell Carcinoma and its 4. Thickness: . mm Variants 5. Mitotic rate: /mm2 6. Excision (circle one) 1. Zimmerman LE. The cancerous, precancerous, Complete and pseudo-cancerous lesions of the cornea and Not complete laterally (indicate affected margins) but complete in depth conjunctiva. In: Rycrfot PV 9ed): Corneoplastic Sur- Not complete in depth but complete laterally gery: Proceedings of the Second International Cor- Not complete either laterally or in depth neoplastic Conference. Oxford: Pergamon Press; 7. Vascular invasion (circle one) Absent 1969:547. Blood vessels 2. Cohen BH, Green WR, Iliff NT, Taxy JB, Schwab Lymphatics WT, de la Cruz Z. Spindle cell carcinoma of the Blood vessels and lymphatics conjunctiva. Arch Ophthalmol 1980;98:1809–13 3. Rao NA, Font RL. Mucoepidermoid carcinoma of the conjunctiva. Cancer 1976;38:1699–709. 2. Jakobiec FA, Folberg R, Iwamoto T. Clinico- pathologic characteristics of premalignant and ma- Conjunctival Malignant Melanoma lignant melanocytic lesions of the conjunctiva. 1. Folberg R, McLean IW, Zimmerman LE. Malig- Ophthalmology 1989;96:147–66. nant melanoma of the conjunctiva. Hum Pathol 3. Seregard S. Conjunctival melanoma. Surv Oph- 1985;16:126–43. thalmol 1998;42:321–50.

728 Modern Pathology TABLE 3. Checklist for Sebaceous Carcinoma, Eyelid TABLE 5. Checklist for Uveal Melanoma and/or Conjunctiva 1. Location (circle all involved) 1. Site Iris 2. Procedure (circle one) Ciliary body Excisional biopsy Choroid Incisional biopsy 2. Extraocular extension: yes no Shave biopsy 3. Growth pattern (circle one) Map biopsy (conjunctiva) Diffuse 3. Lesion is: unifocal multifocal Ring 4. Origin (circle one) Focal Zeis gland 4. Dimension of largest diameter in contact with the sclera: Meibomian gland .mm Both Zeis and Meibomian glands 5. Cell type (Callender classification - circle one) 5. Size (mm) Spindle cell type 6. Infiltrative growth pattern (circle one) Mixed cell type Absent Epithelioid cell type Present Necrotic 7. Pagetoid spread (circle one) 6. Number of mitotic figures per 40ϫ field: . Absent 7. Presence of more than 100 tumor infiltrating lymphocytes per 20 Present high power field (circle one) Present Absent 8. Matrix-rich microcirculation-associated patterns (circle all that apply) TABLE 4. Checklist for Retinoblastoma Nevus-like (normal, avascular, straight, parallel) 1. Site Loops Right eye, left eye Networks 2. Growth pattern (circle one) Parallel vessels with cross-linking Diffuse Unifocal Multi focal 3. Extraocular extension (circle one) Absent Present 3. McLean IW, Rosenberg SH, Messmer EP, et al. 4. Invasion into the optic nerve (circle one) None Prognostic factors in cases of retinoblastoma: anal- Prelaminar ysis of 974 patients from Germany and the United To the lamina scleralis (cribrosa) States treated by enucleation. In: Bornfeld N, Gra- Retrolaminar Posterior resection margin goudas ES, Höpping W, et al. (editors): Tumors of 5. Differentiation (circle all that apply) the Eye. Proceedings of the International Sympo- Poorly differentiated sium on Tumors of the Eye. Amsterdam: Kugler Flexner-Wintersteiner rosettes Home Wright rosettes Publications;1991:69–72. Fleurettes 4. McLean IW, Burnier MN, Zimmerman LE, Ja- kobiec FA. Tumors of the Eye and Ocular Adnexa. Atlas of Tumor Pathology. 3rd Series, Fascicle 12. Washington, DC: Armed Forces Institute of Pathol- 4. Folberg R, Jakobiec FA, McLean IW, Zimmer- ogy, 1994. man LA. Is primary acquired melanosis equivalent to melanoma in situ? Mod Pathol 1992;5:2–5. Uveal Malignant Melanoma 1. Jakobiec FA, Silbert G. Are most iris “melano- Sebaceous Carcinoma of the Eyelid mas” nevi? Arch Ophthalmol 1981;99:2117–32. 1. Rao NA, Hidayat AA, McLean IW, Zimmerman 2. McLean IW, Foster WD, Zimmerman LE, LE. Sebaceous glad carcinoma of the ocular adnexa: Gamel JW. Modifications of Callender’s classifi- a clinicopathologic study of 104 cases with five year cation of uveal melanoma at the Armed Forces follow-up data. Hum Pathol 1982;13:113–22. Institute of Pathology. Am J Ophthalmol 1983;96: 502–9. 3. de la Cruz JR PO, Specht CS, McLean IW. Lym- Retinoblastoma phocytic infiltration in uveal malignant melanoma. 1. Kopelman JE, McLean IW, Rosenberg SH. Mul- Cancer 1990;65:112–5. tivariate analysis of risk factors for metastasis in 4. Folberg R, Rummelt, V, Parys-van Ginder- retinoblastoma treated by enucleation. Ophthal- deuren R, Hwang T, Woolson RF, Pe’er J, Gruman mology 1987;94:371–7. LM. The prognostic value of tumor blood vessel 2. Messmer EP, Heinrich T, Höpping W, de Sutter morphology in primary uveal melanoma. Ophthal- E, Havers W, Sauwerwein W. Risk factors for metas- mology 1993;100:1389–98. tases in patients with retinoblastoma. Ophthalmol- 5. Sorensen FB, Gamel JW, Jensen OA, Ladekarl ogy 1991;98:136–41. M, McCurdy J. Prognostic value of nucleolar size

Reporting Tissues Removed as Part of Surgical Treatment (R. Folberg et al.) 729 and size pleomorphism in choroidal melanomas. 7. Mooy CM, De Jong PTVM. Prognostic param- Aprnis 1993;101:358–68. eters in uveal melanoma: a review. Surv Ophthal- 6. Grossniklaus HE, Oakman JH, Cohen C, Cal- mol 1996;41:215–28. houn FP Jr, De Rose PB, Drews-Botch B. Histopa- 8. Seregard S, Oskarsson M, Spangberg B. PC-10 thology, morphometry, and nuclear DNA content of as a predictor of prognosis after antigen retrieval in iris melanocytic lesions. Invest Ophthalmol Vis Sci posterior uveal melanoma. Invest Ophthalmol Vis 1995;1394:745–50. Sci 1996; 37:1451–8.

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